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Trial record 41 of 126 for:    "Viral Infectious Disease" | "Ethanol"

Modulating the Impact of Critical Events in Early HIV Infection: Effect of ART Initiation and Alcohol Use (MERLIN)

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ClinicalTrials.gov Identifier: NCT02744040
Recruitment Status : Recruiting
First Posted : April 20, 2016
Last Update Posted : November 12, 2018
Sponsor:
Collaborators:
University of California, San Francisco
University of Washington
Asociación Civil Impacta Salud y Educación, Peru
Université de Montréal
Seattle Children's Hospital
Information provided by (Responsible Party):
Ann C Duerr, Fred Hutchinson Cancer Research Center

Brief Summary:

The overall objective is to determine the influence of timing of ART initiation and alcohol consumption on HIV disease course, including detailed analysis of important events occurring shortly after HIV acquisition. ART initiation immediately after HIV infection (during Fiebig stages I-II) largely results in smaller HIV reservoir and lower HIV-associated systemic inflammation, which has been linked to non-AIDS morbidity and mortality. Immediate ART also reduces HIV-associated bacterial translocation and may prevent dysbiosis, an alteration of the intestinal microbiota that has been linked to increased systemic inflammation. Immediate intervention is not, however, generally feasible and more information is required about the consequences of starting ART at later time-points, but still early after acquisition. The proposed study will be conducted in Lima, Peru, in the cohort of 180 MSM with acute (Ab-, HIV RNA+) or recent (≤ 3 months) HIV infection. Alcohol use disorder is present in ~50% of HIV-infected MSM in our cohort, which is four times higher than that seen among males in the general Peruvian population. Although the role of alcohol use in HIV pathogenesis and disease course remains unclear, some studies show a correlation with accelerated disease progression. In animal models and clinical studies, both acute and chronic alcohol consumption have been linked to bacterial translocation and activation of the innate immune system, which can lead to increases in pro-inflammatory cytokines. The effects of alcohol resemble early post-infection changes in bacterial translocation and pro-inflammatory cytokines induced by HIV and their impact on HIV disease course before and after ART initiation remain unexplored.

Specific Aim 1: To determine the relative long-term benefits of immediate vs. early vs. delayed ART initiation. The investigators will study outcomes after 1.5 and 3.5 years in MSM diagnosed with acute or recent HIV infection. The investigators will examine outcomes in 3 groups based on time of ART initiation: a) immediate: during FI-II (N~30), b) early: during FIII-V (N~50) or c) delayed: at 24 weeks after diagnosis (N~80). The investigators anticipate that CD4+ T cell counts and peripheral inflammatory markers in the FIII-V group and the delayed group will approach those in the immediate treatment group (FI-II) over time; in contrast, they expect that those started ART at "early" or "delayed" time points will have persistent changes in the GI microbiome and in the HIV reservoir.

Specific Aim 2: To determine the impact of alcohol use on the relative long-term benefits of immediate vs. early vs. delayed initiation of ART. The investigators will examine the impact of alcohol use on critical events in HIV infection. They hypothesize that dose-dependent alcohol-induced changes will compound the negative effects of HIV and lead to greater levels of dysbiosis and inflammation, higher early plasma HIV RNA, and greater "seeding" and persistence of HIV DNA in participants with high-level alcohol use. The investigators will assess viral load, GI microbiome and metagenomics, pro-inflammatory cytokines, production of msRNA and analyze the impact on alcohol use in all subjects prior to ART initiation and among ART-adherent participants with persistent viral suppression.


Condition or disease Intervention/treatment Phase
HIV Infection Drug: ART initiation at time of HIV diagnosis Drug: ART at 24 weeks Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Modulating the Impact of Critical Events in Early HIV Infection: Effect of ART Initiation and Alcohol Use
Actual Study Start Date : August 28, 2017
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Alcohol HIV/AIDS

Arm Intervention/treatment
Early ART initiation
Immediate ART initiation at the time of HIV diagnosis; daily dose of combination ART (one pill/day)
Drug: ART initiation at time of HIV diagnosis
Immediate ART initiation

Deferred ART initiation
ART initiation at 24 weeks after HIV diagnosis; daily dose of combination ART (one pill/day)
Drug: ART at 24 weeks
ART initiation 24 weeks after enrollment




Primary Outcome Measures :
  1. HIV reservoir [ Time Frame: 3.5 years ]
    HIV reservoir measured a several time points after ART initiation


Secondary Outcome Measures :
  1. GI microbiome [ Time Frame: 3.5 years ]
    GI microbiome characterized at multiple time points after ART initiation

  2. DNA integration sites [ Time Frame: 3.5 years ]
    HIV integration sites measured after 3 1/2 years of VL suppression on ART



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men who have sex with men or transgender women HIV-infected with prior participation in SABES study in Lima Peru OR Established HIV infection OR HIV uninfected

Exclusion Criteria:

  • counter-indication for use of study antiretroviral drugs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02744040


Contacts
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Contact: Ann C Duerr, MD, PhD, MPH 206 667 7938 aduerr@fredhutch.org
Contact: Delia Pinto-Santini, PhD 206 667 7858 psantini@fredhutch.org

Locations
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Peru
Asociación Civil Impacta Salud y Educación Recruiting
Lima, Peru
Contact: Javier Lama, MD, MPH       jrlama@impactaperu.org   
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
University of California, San Francisco
University of Washington
Asociación Civil Impacta Salud y Educación, Peru
Université de Montréal
Seattle Children's Hospital
Investigators
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Principal Investigator: Ann Duerr Fred Hutchinson Cancer Research Center

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Responsible Party: Ann C Duerr, Member, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT02744040     History of Changes
Other Study ID Numbers: R01DA040532-01 ( U.S. NIH Grant/Contract )
First Posted: April 20, 2016    Key Record Dates
Last Update Posted: November 12, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Ann C Duerr, Fred Hutchinson Cancer Research Center:
HIV reservoir
alcohol
ART
Additional relevant MeSH terms:
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RNA Virus Infections
Virus Diseases
Slow Virus Diseases
Ethanol
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs